Copper catalyzed oxidation of alzheimer A beta

Citation
Cs. Atwood et al., Copper catalyzed oxidation of alzheimer A beta, CELL MOL B, 46(4), 2000, pp. 777-783
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELLULAR AND MOLECULAR BIOLOGY
ISSN journal
0145-5680 → ACNP
Volume
46
Issue
4
Year of publication
2000
Pages
777 - 783
Database
ISI
SICI code
0145-5680(200006)46:4<777:CCOOAA>2.0.ZU;2-X
Abstract
A beta derived from amyloid plaques of Alzheimer's disease-affected brain c ontain several oxidative posttranslational modifications. In this study we have characterized the amino acid content of human amyloid-derived A beta a nd compared it with that of human synthetic A beta subjected to metal-catal yzed oxidation. Human amyloid derived A beta has an increased content of ar ginine (46%) and glutamate/glutamine residues (28%), but a decreased conten t of histidine residues (-32%) as compared to the expected amino acid conte nt. Incubation of synthetic human A beta with Cu(II), but not Fe(III), in t he presence of H2O2 similarly induced a decrease in histidine residues (-79 %), but also a decrease in tyrosine residues (-28%). Our results suggest th at histidine and tyrosine are most vulnerable to metal mediated oxidative a ttack, consistent with our earlier findings that Cu coordinated via histidi ne residues is redox competent. Our results suggest that the loss of histid ine residues in human amyloid-derived A beta may be a result of Cu oxidatio n, and that unidentified post-translational mechanisms operate to modify ot her amino acids of A beta in vivo.